Dr.
Lengsfeld’s Biofluids Laboratory is fundamentally interested in the
forces that hydrodynamic flows impart on particles and material
surfaces. This many included developing forces to oppose particle
deposition in mechanical ventilators, correlating the probability
of
fragmentation with turbulent length scale,
manufacturing of non-viral vectors via directed self assembly
techniques, simulating the contribution of
fluid flow in joint mechanics, and even developing remote sensor
systems to monitor drug interactions in the aging population. Our goal
is to lower the costs associated with manufacturing and delivering
therapeutics while maintaining or increasing efficacy.

Shear
Induced Degradation of DNATherapeutic
DNA and siRNA offer the potential to cure many genetic diseases. In
contrast to traditional
small-molecule drugs, biopharmaceuticals possess secondary structure
that maybe damaged during one of many bioprocessing steps.
Our research has determined that hydrodynamic degradation pathways
dominate plasmid, cosmid and genomic DNA fragmentation during
aerosolization and pipe flow. This loss of molecular structure can be
attributed to turbulent length scales at or below the molecules length
as well as localized cavitation events. Based on these findings we have
set forth a series of guidelines for chosing aerosolization devices for
the pulmonary delivery of genetic theraputics as well as bioprocessing
guidelines to limit the contamination of genomic DNA during
bioprocessing. Finally this project designed several mitigation
techniques for classical atomizers and put forth a new safe and
effective aerosolization technique for consideration. We
gratefully acknowledge the financial support for this work from two NSF
collaborative grants (BES-0214015 and BES-0239940)
and recognize the collaboration of the University of Colorado School of
Pharmacy. In addition, some equipment donations were obtained from
Bohlin and ADA Technology.

Improved
Synthetic Vectors by Electrostatic Co-Extrusion:The evolution of gene therapy has been hindered by the
development of safe and effective delivery vectors. Electrostatic
co-extrusion (a platform technology currently under patent by our lab)
to manufacture non-viral vectors.
This manufacturing process from provides control over particle size and
size distribution from micron to the nano scale. The technique provides
100% encapsulation efficiency and enables the use of neutral lipids. We
are currently investigating the limitations of molecular stability as a
function of electric potential gradient and charge density. We
gratefully acknowledge the financial support for this work from two NSF
collaborative grants (BES-0433810 and
BES-0433811) and recognize the
collaboration of the University of Colorado School of
Pharmacy.

Pulmonary
drug
delivery to patients on mechanical ventilators currently resides around
5% of the intended dose. Applying humidity to an
airflow before it enters a jet nebulizer increases Salbutamol
deposition in the lung. This addition of humidity is a relatively
simple, yet
effective way
to improve drug delivery. This finding becomes especially relevant when
noting that
mechanically ventilated patients generally must have some kind of
humidity
applied to their ventilator system.
Conventional methods of applying humidity (i.e. through the corrugated
tubing prior to a nebulization tee)
decrease Salbutamol deposition in the deep lung due to particle growth
by condensation, but applying humidity to the airflow entering the
nebulizer
appears to
increase drug deposition in the lung. Despite the increases seen
in the
Salbutamol deposition in the deep lung, the corresponding increases in
the
amount of drug exhaled in this process is the next obvious place for
improvement with this technique. This work was funded by a PROF
grant from the University of Denver and equipment donations are
gratefully acknowledged from Pulmonetic Systems Inc., Michigan
Instruments and Ocean Optics.

Wearable sensor technologies:We have developed an
sensor system that fits with the insole of a shoe and communicates gait
data wirelessly to a base station. The system is currently under
evaluation as a tool to detect variations in gait. We
gratefully acknowledge the financial support for this work from the US Department
of Health and Human Services and the University of Denver Partners in
Scholarship program. Further we recognize the collaborative efforts of
the University of Colorado Center on Aging.

Developing a fluidic
system to evaluate environment pressures on gene mutations

Largely through widespread sanitation and use of
antibiotics, bacterial infectious diseases have exerted a greatly
decreased influence on the health and lifespan of the developed
world’s population. In contrast, these diseases have continuously
impacted the developing world’s population. With the
increasing emergence of new antibiotic-resistant strains and the
weaponization of normally rare bacterial strains, the threat of
pandemic disease and its fall-out on the developed world has
re-emerged. Recognition of this threat has engendered efforts to
address prevention and cure of these diseases, as well as the study
of the complex interaction between the host, pathogen, and
environmental factors that impact the progression and severity of
the disease. By exploiting the advances in fluidics and
materials engineering, we propose to create a system to rapidly and
simultaneously interrogate the myriad of culture conditions
necessary for successful cultivation of target organisms. We
gratefully acknowledge the financial support for this work from the
Keck Foundation in collaboration with the National Academies of
Science and Engineering.

Education:Postdoc Chemical
Engineering, University of Colorado at Boulder (July 1997 to August
1999) Ph.D.
Mechanical Engineering, University of California at Irvine (June 1997) M.S.
Mechanical Engineering, University of California at Irvine (December
1993) B.S.
Mechanical Engineering, University of California at Irvine (June 1992)